Genetic Variations of FSH Receptor Gene in Patients with Premature Ovarian Failure and Diminished Ovarian Reserve Referred to Royan Institute

Headnote

Keywords: Follicle Stimulating Hormone Receptor, Polymorphisms, Inactivating Mutations, Premature Ovarian Failure, Diminished Ovarian Reserve

Background: Immaturity of the ovarian follicles results in an infertility citation called Premature Ovarian Failure (POF), affecting approximately 1% of women under the age of 40. Women with this disorder go through early menopause and have high levels of gonadotropin hormones (FSH & LH). Diminished Ovarian Reserve (DOR) is another infertility disorder in which women's ovaries have the ability to go through early menopause. On the other hand, follicle stimulating hormone has a critical role in the maturation of the ovarian follicles. FSH will start a signaling cascade in the granulosa cells after sitting on its receptor. Inactivating of this receptor may arrest follicle maturation and therefore result in POF development.

Materials and Methods: The presence of 566C>T, 1555C>A and 1043C>G inactivating mutations and 1572C>G and 1993A>G polymorphisms were analyzed in a case control study. 43 Iranian POF and 27 Iranian DOR patients who had been referred to Royan Institute and had high levels of FSH hormone, normal karyotype and wild type FMR1 gene were selected as the case group. 40 Iranian fertile women were enrolled as the control group. The patients DNA were extracted from their peripheral blood and amplified by relevant primers. For determining allelic variant status, RFLP and SSCP with Sequencing were done with the amplified PCR products.

Results: Wild type genotype was seen in all cases. A common polymorphism (919G>A) was seen in all three groups. There was no significant difference between them. Hence no inactivating mutations were seen in Iranian POF and DOR patients.

Conclusion: Although these mutations and polymorphisms, especially 566C>T were seen in some other populations, this study showed that FSHR gene inactivating mutations and polymorphisms are not frequent in Iranian POF and DOR patients.